A two stage, open-label, phase II trial assessing the efficacy of a single oral agent AZD4547 in malignant mesothelioma.
- Conditions
- Malignant MesotheliomaCancer - Lung - MesotheliomaCancer - Other cancer types
- Registration Number
- ACTRN12615001291572
- Lead Sponsor
- Institute of Respiratory Health
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- All
- Target Recruitment
- 24
Histologically or cytologically malignant pleural mesothelioma
1.Provision of signed and dated, written informed consent prior to any study specific procedures.
2.Male or female aged 25 years or older.
3.Histologically or cytologically confirmed diagnosis of mesothelioma.
4.Progression after first line chemotherapy with pemetrexed and a platinum-based drug (cisplatin and/or carboplatin).
5.Evidence of measurable disease. Measurable disease must be outside a previous radiotherapy field, unless it has been documented to progress after radiotherapy.
6.ECOG performance status 0-1, minimum life expectancy of 12 weeks from proposed first dose date, no deterioration within 2 weeks of screening and first dose.
7.Females should be using adequate contraceptive measures (see restrictions), should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
*Post-menopausal defined as:
a.Aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
b.Aged under 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments and with LH and FSH levels in the postmenopausal range.
*Documentation of irreversible surgical sterilisation by hysterectomy, and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal ligation.
8.Male patients should be willing to use barrier contraception, ie condoms.
1.Any prior chemotherapy other than pemetrexed and a platinum compound.
2.Concurrent treatment with any experimental drugs or other anti-cancer therapy.
3.Prior exposure to any of the following: Prior exposure to an FGFR inhibitor and/orPrior treatment in this or another AZD4547 study, or randomisation in a study in which AZD4547 is/was under investigation.
-AZD4547 in the present study (ie, dosing with AZD4547 previously initiated in this study).
-Potent inhibitors or inducers of CYP3A4, inhibitors of CYP2D6 or substrates of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St John’s Wort). Refer to Section 7.7 of this document for an example list of applicable drugs.
-Any chemotherapy, immunotherapy or anticancer agents within 3 weeks before the first dose of study treatment.
-Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment.
-Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks before the first dose of study treatment.
-Other concomitant anti-cancer therapy except corticosteroids.
4.Any of the following ophthalmological criteria:
-Current evidence or previous history of RPED.
-Previous laser treatment or intra-ocular injection for treatment of macular degeneration.
-Current evidence or previous history of dry or wet age-related macular degeneration.
-Current evidence or previous history of retinal vein occlusion.
-Current evidence or previous history of retinal degenerative diseases (eg, hereditary).
-Current evidence or previous history of any other clinically relevant chorioretinal defect.
5.Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD4547.
6.With the exception of alopecia, any unresolved toxicities from prior therapy with a Common Terminology Criteria for Adverse Events (CTCAE) grade >1 at the time of starting study treatment.
7.As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
8.Any of the following cardiac criteria:
-Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 consecutive electrocardiograms (ECGs).
-Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block.
-Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval.
9.Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
-Absolute neutrophil count < 1.5 x 109/L.
-Platelet count < 100 x 109/L.
-Haemoglobin < 90 g/L (can be transfused to meet inclusion criterion).
-Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases/invasion or > 5 times ULN in the presence of liver metastases or liver invasion
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method